T-cell mediated lympholysis (CML) was generated in vitro against syngeneic murine spleen cells conjugated with three different haptens: trinitrophenyl (TNP-self), fluorescein isothiocyanate (FITC-self) and 1,5 I-AEDANS (AEDANS-self). Genetic control of CML responses to these three haptens was observed. H-2k,a and H-2b,d mouse strains were the respective genetic high and low responders to TNP-self and FITC-self, both of which conjugate the epsilon-NH2 groups. The reverse genetic pattern was observed for CTL responses to AEDANS-self which conjugates with -SH groups. These differential response patterns raise some interesting possibilities concerning genetic control of immune responses and the self determinants recognized.